The purpose of this Animal Core is to perform and monitor gene therapy studies in dog models of human hemophilia A, hemophilia B, and F.VII deficiency for the scientific investigations proposed in Projects 1 through 3. To date, successful gene therapy in hemophilic dogs has resulted in long-term (from 1 to >10 years) expression of plasma factors Vlll (F.VIII), IX (F.IX), and F.Vila and many of these dogs have exhibited a lower toxicity issues have been detected to date. These studies have also highlighted the limitations in gene therapy including low levels of transgene expression, dose thresholds for inhibitory antibody formation, and the relative paucity of strategies for hemophilia patients with inhibitory antibodies. These limitations and other critical issues in hemophilia gene therapy are addressed in this PPG. In the next grant period, a novel ultrasound based test entitled "Acoustic Radiation Force Impulse" imaging will be validated as a hemostatic challenge and used as an additional tool to monitor hemostatic efficacy of the various gene transfer protocols. Please note that this Core will support the gene transfer experiments and the experimental animals (those receiving gene transfer) that will be housed and monitored at the Francis Owen Blood Research Laboratory (FOBRL) at the University of North Carolina at Chapel Hill. The non-experimental animals (breeders, substrate and normal plasma donors, etc.) will largely be supported by an NHLBI-funded Resource Grant (R24-HL63098) entitled "Maintenance of Animal Models of Hemophilia and VWD," Timothy C. Nichols P.l.